Immunogenicity and Protective Potential of Mucosal Vaccine Formulations Based on Conserved Epitopes of Influenza A Viruses Fused to an Innovative Ring Nanoplatform in Mice and Chickens.

Current inactivated vaccines against influenza A viruses (IAV) mainly induce immune responses against highly variable epitopes across strains and are mostly delivered parenterally, limiting the development of an effective mucosal immunity. In this study, we evaluated the potential of intranasal formulations incorporating conserved IAV epitopes, namely the long alpha helix (LAH) of the stalk domain of hemagglutinin and three tandem repeats of the ectodomain of the matrix protein 2 (3M2e), as universal mucosal anti-IAV vaccines in mice and chickens. The IAV epitopes were grafted to nanorings, a novel platform technology for mucosal vaccination formed by the nucleoprotein (N) of the respiratory syncytial virus, in fusion or not with the C-terminal end of the P97 protein (P97c), a recently identified Toll-like receptor 5 agonist. Fusion of LAH to nanorings boosted the generation of LAH-specific systemic and local antibody responses as well as cellular immunity in mice, whereas the carrier effect of nanorings was less pronounced towards 3M2e. Mice vaccinated with chimeric nanorings bearing IAV epitopes in fusion with P97c presented modest LAH- or M2e-specific IgG titers in serum and were unable to generate a mucosal humoral response. In contrast, N-3M2e or N-LAH nanorings admixed with Montanide™ gel (MG) triggered strong specific humoral responses, composed of serum type 1/type 2 IgG and mucosal IgG and IgA, as well as cellular responses dominated by type 1/type 17 cytokine profiles. All mice vaccinated with the [N-3M2e + N-LAH + MG] formulation survived an H1N1 challenge and the combination of both N-3M2e and N-LAH nanorings with MG enhanced the clinical and/or virological protective potential of the preparation in comparison to individual nanorings. Chickens vaccinated parenterally or mucosally with N-LAH and N-3M2e nanorings admixed with Montanide™ adjuvants developed a specific systemic humoral response, which nonetheless failed to confer protection against heterosubtypic challenge with a highly pathogenic H5N8 strain. Thus, while the combination of N-LAH and N-3M2e nanorings with Montanide™ adjuvants shows promise as a universal mucosal anti-IAV vaccine in the mouse model, further experiments have to be conducted to extend its efficacy to poultry.

In-Orbit Attitude Determination of the UVSQ-SAT CubeSat Using TRIAD and MEKF Methods.

Ultraviolet and infrared sensors at high quantum efficiency on-board a small satellite (UVSQ-SAT) is a CubeSat dedicated to the observation of the Earth and the Sun. This satellite has been in orbit since January 2021. It measures the Earth's outgoing shortwave and longwave radiations. The satellite does not have an active pointing system. To improve the accuracy of the Earth's radiative measurements and to resolve spatio-temporal fluctuations as much as possible, it is necessary to have a good knowledge of the attitude of the UVSQ-SAT CubeSat. The attitude determination of small satellites remains a challenge, and UVSQ-SAT represents a real and unique example to date for testing and validating different methods to improve the in-orbit attitude determination of a CubeSat. This paper presents the flight results of the UVSQ-SAT's attitude determination. The Tri-Axial Attitude Determination (TRIAD) method was used, which represents one of the simplest solutions to the spacecraft attitude determination problem. Another method based on the Multiplicative Extended Kalman Filter (MEKF) was used to improve the results obtained with the TRIAD method. In sunlight, the CubeSat attitude is determined at an accuracy better than 3° (at one σ) for both methods. During eclipses, the accuracy of the TRIAD method is 14°, while it reaches 10° (at one σ) for the recursive MEKF method. Many future satellites could benefit from these studies in order to validate methods and configurations before launch.

Robust Detection of Somatic Mosaicism and Repeat Interruptions by Long-Read Targeted Sequencing in Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is the most complex and variable trinucleotide repeat disorder caused by an unstable CTG repeat expansion, reaching up to 4000 CTG in the most severe cases. The genetic and clinical variability of DM1 depend on the sex and age of the transmitting parent, but also on the CTG repeat number, presence of repeat interruptions and/or on the degree of somatic instability. Currently, it is difficult to simultaneously and accurately determine these contributing factors in DM1 patients due to the limitations of gold standard methods used in molecular diagnostics and research laboratories. Our study showed the efficiency of the latest PacBio long-read sequencing technology to sequence large CTG trinucleotides, detect multiple and single repeat interruptions and estimate the levels of somatic mosaicism in DM1 patients carrying complex CTG repeat expansions inaccessible to most methods. Using this innovative approach, we revealed the existence of de novo CCG interruptions associated with CTG stabilization/contraction across generations in a new DM1 family. We also demonstrated that our method is suitable to sequence the DM1 locus and measure somatic mosaicism in DM1 families carrying more than 1000 pure CTG repeats. Better characterization of expanded alleles in DM1 patients can significantly improve prognosis and genetic counseling, not only in DM1 but also for other tandem DNA repeat disorders.

Atmospheric Correction Inter-comparison eXercise.

The Atmospheric Correction Inter-comparison eXercise (ACIX) is an international initiative with the aim to analyse the Surface Reflectance (SR) products of various state-of-the-art atmospheric correction (AC) processors. The Aerosol Optical Thickness (AOT) and Water Vapour (WV) are also examined in ACIX as additional outputs of an AC processing. In this paper, the general ACIX framework is discussed; special mention is made of the motivation to initiate this challenge, the inter-comparison protocol and the principal results. ACIX is free and open and every developer was welcome to participate. Eventually, 12 participants applied their approaches to various Landsat-8 and Sentinel-2 image datasets acquired over sites around the world. The current results diverge depending on the sensors, products and sites, indicating their strengths and weaknesses. Indeed, this first implementation of processor inter-comparison was proven to be a good lesson for the developers to learn the advantages and limitations of their approaches. Various algorithm improvements are expected, if not already implemented, and the enhanced performances are yet to be investigated in future ACIX experiments.

Generalized ocean color inversion model for retrieving marine inherent optical properties.

Ocean color measured from satellites provides daily, global estimates of marine inherent optical properties (IOPs). Semi-analytical algorithms (SAAs) provide one mechanism for inverting the color of the water observed by the satellite into IOPs. While numerous SAAs exist, most are similarly constructed and few are appropriately parameterized for all water masses for all seasons. To initiate community-wide discussion of these limitations, NASA organized two workshops that deconstructed SAAs to identify similarities and uniqueness and to progress toward consensus on a unified SAA. This effort resulted in the development of the generalized IOP (GIOP) model software that allows for the construction of different SAAs at runtime by selection from an assortment of model parameterizations. As such, GIOP permits isolation and evaluation of specific modeling assumptions, construction of SAAs, development of regionally tuned SAAs, and execution of ensemble inversion modeling. Working groups associated with the workshops proposed a preliminary default configuration for GIOP (GIOP-DC), with alternative model parameterizations and features defined for subsequent evaluation. In this paper, we: (1) describe the theoretical basis of GIOP; (2) present GIOP-DC and verify its comparable performance to other popular SAAs using both in situ and synthetic data sets; and, (3) quantify the sensitivities of their output to their parameterization. We use the latter to develop a hierarchical sensitivity of SAAs to various model parameterizations, to identify components of SAAs that merit focus in future research, and to provide material for discussion on algorithm uncertainties and future emsemble applications.

Detection and estimation trends linked to air quality and mortality on French Riviera over the 1990-2005 period.

There is a profound relation between human health and well being from the one side and air pollution levels from the other. Air quality in South of France and more specifically in Nice, is known to be bad, especially in summer. The non-parametric Mann-Kendall test has been developed for detecting and estimating monotonic trends in the time series and applied in our study at annual values of pollutants air concentrations and mortality. An important objective of many environmental monitoring programs is to detect changes or trends in pollution levels over time. Over the period 1990-2005, concerning the emissions of main pollutants, we obtained significant decreasing trends. By considering the ozone mean values in urban areas over the 1997-2005 period, an increase of 3.0% year(-1) was obtained with annual averages and 3.9% year(-1) with median values. A clear increasing trend for PM(10) ambient concentrations is obtained. In addition, we observed an increase of the Olea (and Grass) pollination season. Over the same period, an annual change rate of +0.31% year(-1) for "airway diseases" and of +2.50% year(-1) for "unknown causes" were identified in the "Alpes Maritimes" county. To see the results, there seems to be a short-term link between the levels of these pollutants and mortality for respiratory causes. The other pollutants concentration showed a downward trend reflecting the reduction policy of the emissions. In addition, we obtained significant decreasing trends concerning the "ischemic heart diseases" (-1.20% year(-1)) and "asthma" (-4.03% year(-1)) categories. No significant gender-related difference was identified for these groups.